Haemolysis due to drugs and chemicals

This can be caused by :

1. Direct toxic action.
    -> Naphthalene.
    -> Nitrobenzene.
    -> Phenacetin.
    -> Lead.

Heinz bodies are seen in abundance.

2. Drug action on G-6-PD deficient RBC
3. Immunological mechanism which may be : 
    -> Drug induced  autoantibody haemolysis, Antibodies are directed against RBC.
    -> Hapten-cell mechanism where antibodies are directed against which is bound to cell surface e.g. Penicilin.
 

Chronic myelocytic leukaemia
Commoner in adults (except the Juvenile type)

Features:

- Anaemia.
- Massive splenomegaly
- Bleeding tendencies.
- Sternal tenderness.
- Gout and skin manifestations

Blood picture:

- Marked leucocytosis of 50,-1000,000 cu.mm, often more
- Immature cells of the series with 20-50 % myelocytes
- Blasts form upto 5-10% of cells
- Basophils may be increased
- Leuocyte alkaline phosphate is reduced
- Anaemia with reticutosis and nucleated RBC
- Platelets initially high levels may fall later if patient goes into blast crisis.

Bone marrow:
- Hyper cellular marrow.
- Myeloid hyperplasia with more of immature forms, persominatly myelocytes.

Chromosomal finding. Philadelphia (Phi) chromosome is positive adult cases .It is a short chromosome due to deletion  of long arm of chromosome 22 (translocated to no.9),

Juvenile type :- This is Ph1 negative  has more nodal enlargement and has a worse prognosis, with a greater proneness to infections and haemorrhage
 

Osteonecrosis (Avascular Necrosis) 

Ischemic necrosis with resultant bone infarction occurs mostly due to fracture or after corticosteroid use. Microscopically, dead bon trabevulae (characterized by empty lacunae) are interspersed with areas of fat necrosis.

The cortex is usually not affected because of collateral blood supply; in subchondral infarcts, the overlying articular cartilage also remains viable because the synovial fluid can provide nutritional support. With time, osteoclasts can resorb many of the necrotic bony trabeculae; any dead bone fragments that remain act as scaffolds for new bone formation, a process called creeping substitution.

Symptoms depend on the size and location of injury. Subchondral infarcts often collapse and can lead to severe osteoarthritis. 

Multiple sclerosis
a. A demyelinating disease that primarily affects myelin (i.e. white matter). This affects the conduction of electrical impulses along the axons of nerves. Areas of demyelination are known as plaques.
b. The most common demyelinating disease.
c. Onset of disease usually occurs between ages 20 and 50; slightly more common in women.
d. Disease can affect any neuron in the central nervous system, including the brainstem and spinal cord. The optic nerve (vision) is commonly affected.

Primary vs. secondary disorders - Most nutritional disorders in developed countries are not due to simple dietary deficiencies but are rather a secondary manifestation of an underlying primary condition or disorder.

• Chronic alcoholism
• Pregnancy and lactation
• Renal dialysis
• Eating disorders
• Prolonged use of diuretics
• Malabsorption syndromes
• Neoplasms
• Food fads
• Vegans
• AIDS 

Megaloblastic anaemia

Metabolism: B12(cyanocobalamin) is a coenzyme in DNA synthesis and for maintenance of nervous system. Daily requirement 2 micro grams. Absorption in terminal ileum in the presence gastric intrinsic factor. It is stored in liver mainly-

Folic acid (Pteroylglutamic acid) is needed for DNA synthesis.. Daily requirement 100 micro grams. Absorption in duodenum  and jejunum

Causes of deficiency .-

- Nutritional deficiency-
- Malabsorption syndrome.
- Pernicious anaemia (B12).
- Gastrectomy (B12).
- Fish tapeworm infestation (B12).
- Pregnancy and puerperium (Folic acid mainly).
- Myeloproliferative disorders (Folic acid).
- Malignancies (Folic acid).
- Drug induced (Folic-acid)

Features:

(i) Megaloblastic anaemia.
(ii) Glossitis.
(iii) Subacute combined degeneration (in B12deficiency).

Blood picture :

- Macrocytic normochromic anaemia.
- Anisocytosis and poikilocytosis with Howell-Jolly bodies and  basophilic stippling.
- Occasional megalo blasts may be-seen.
- Neutropenia with hypersegmented neutrophills and macropolycytes.
- Thrombocytopenia.
- Increased MVC and MCH with normal or decreased MCHC.

Bone marrow:

- Megaloblasts are seen. They are larger with a more open stippled chromatin. The nuclear maturation lags behind. the cytoplasmic maturation. Maturation arrest is seen (more of early forms).
- Immature cells of granulocyte series are also larger.
 -Giant stab forms (giant metamyelocytes).